Adrenergic Receptor Mechanisms of Functional Sympatholysis in the Regulation of Regional Blood Flow in Response to Epinephrine After 5-Day Cold Acclimation

BACKGROUND: Muscle contraction is accompanied by an increase in blood flow by several tens of times due to the mechanisms of sympatholysis. However, no studies have quantitatively described the effect of epinephrine on arterial alpha-adrenergic receptors during sympatholysis under conditions of 5-day cold acclimation. AIM: To investigate the impact of 5-day cold acclimation on the adrenoreactivity of arterial vessels in muscles during sympatholysis in response to various doses of epinephrine. METHODS: The study involved four groups of rabbits: a control group (N1, n=20); a sympatholysis group (N2, n=15) with electrical muscle stimulation (5 Hz, 10 V, L=5 ms) to induce sympatholysis; a cold acclimation group (N3, n=15) exposed for five days in a climate chamber (−10 °C, 6 h/day); and a group of rabbits subjected to a combination of 5-day cold acclimation and sympatholysis (N4, n=15). In all animals, after ligation of all anastomoses, arterial blood was perfused into the limb muscles through the femoral artery using a constant-flow pump. Following administration of eight doses of epinephrine (0.5–30 µg/kg), adrenoreactivity of the limb arteries was assessed based on dose–response analysis in Lineweaver–Burk double reciprocal coordinates. This allowed determination of the number of active adrenergic receptors (Pm) and their sensitivity (1/Km) to epinephrine. RESULTS: Sympatholysis after 5-day cold acclimation (N4) was markedly lower at all doses of epinephrine than under non-cold conditions (N2), which indicated a reduction in blood flow in working muscles during sympatholysis in the context of cold exposure. Analysis in Lineweaver–Burk double reciprocal coordinates revealed that, during sympatholysis after cold exposure, the number of active alpha-adrenergic receptors increased 1.407-fold (by 40.7%) to Pm=312.5 mmHg, compared to Pm=222 mmHg during sympatholysis without cold exposure. Simultaneously, after cold exposure (N4), the sensitivity (1/Km) of alpha-adrenergic receptors to epinephrine during sympatholysis increased 1.632-fold (by 63.2%) to 1/Km=0.08, compared to 1/Km=0.049 during sympatholysis without cold exposure (N2). Complete attenuation of sympatholysis at 30 µg/kg epinephrine after cold acclimation confirmed the critical role of dose-dependent pharmacokinetics in arterial tone regulation under cold stress. CONCLUSION: Based on the obtained data, it can be concluded that sympatholysis is preserved after five days of cold exposure, but occurs to a lesser extent than without cold exposure. The enhanced adrenergic vasoconstriction after five days of cold exposure improves heat conservation but compromises blood flow in working muscles, thereby limiting physical performance. These mechanisms may underlie the phenomenon of “early cold asthenia” in individuals with short-term Arctic exposure, characterized by reduced physical exercise tolerance despite preserved basal hemodynamic homeostasis. © 2025 Elsevier B.V., All rights reserved.